Zydelig is indicated, in combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

Tablets:

Zydelig is contraindicated in patients with a history of serious hypersensitivity reactions to idelalisib, including anaphylaxis, or patients with a history of toxic epidermal necrolysis with any drug

The following clinically significant adverse reactions are described elsewhere in the labeling.

Idelalisib is a kinase inhibitor. The chemical name for idelalisib is 5-fluoro-3-phenyl-2-[(1S)-1-(

Idelalisib is a white to off-white solid with a pH-dependent aqueous solubility ranging from <0.1 mg/mL at pH 5–7 to over 1 mg/mL at pH 2 under ambient conditions.

Zydelig (idelalisib) tablets are for oral use. Each tablet contains either 100 mg or 150 mg of idelalisib with the following inactive ingredients: microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, sodium starch glycolate, magnesium stearate and a tablet coating. The tablet coating consists of polyethylene glycol, talc, polyvinyl alcohol, and titanium dioxide and of FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake (for the 100 mg tablet) and red iron oxide (for the 150 mg tablet).

Zydelig was evaluated in a randomized, double-blind, placebo-controlled study GS-US-312-0116 (referred to as 312-0116) (NCT01539512) in 220 patients with relapsed CLL who required treatment and were unable to tolerate standard chemoimmunotherapy due to coexisting medical conditions, reduced renal function as measured by creatinine clearance < 60 mL/min, or NCI CTCAE Grade ≥ 3 neutropenia or Grade ≥ 3 thrombocytopenia resulting from myelotoxic effects of prior therapy with cytotoxic agents. Patients were randomized 1:1 to receive 8 doses of rituximab (first dose at 375 mg/m

The median age was 71 years (range 47, 92) with 78% over 65, 66% were male, and 90% were White. The median time since diagnosis was 8.5 years. The median number of prior therapies was 3. Nearly all (96%) patients had received prior anti-CD20 monoclonal antibodies. The most common (>15%) prior regimens were: bendamustine + rituximab (BR) (98 patients, 45%), fludarabine + cyclophosphamide + rituximab (75 patients, 34%), single-agent rituximab (67 patients, 31%), fludarabine + rituximab (37 patients, 17%), and chlorambucil (36 patients, 16%). The median CIRS (Cumulative Illness Rating Scale) score was 8 (range 0–17), and 85% of patients had a score of >6. Median Karnofsky score was 80. Median estimated Creatinine Clearance (eCLcr) was 63.6 mL/min, with 41% of patients having an eCLcr of <60 mL/min. At screening, 19.5% of patients had a platelet count of <50 × 10

The efficacy of Zydelig was based on progression free survival (PFS), as assessed by an independent review committee (IRC). The trial was stopped for efficacy following the first pre-specified interim analysis. Results of a second interim analysis continued to show a statistically significant improvement for Zydelig + R compared to placebo + R for the major efficacy outcome measure of PFS (HR: 0.18, 95% CI [0.10, 0.32], p <0.0001).

At the final analysis, with a median follow-up of 8.3 months for the Zydelig + R group, and 5.6 months for the placebo + R group, the median PFS for the Zydelig + R group was 19.4 months (95% CI: 12.3, Not Reached) versus 6.5 months (95% CI: 4.0, 7.3) for the placebo + R group (HR: 0.15, 95% CI [0.09, 0.24], p < 0.0001).

Updated efficacy results are shown in Table 7 and the Kaplan-Meier curve for PFS is shown in Figure 1.

Zydelig tablets supplied as follows:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

NDC 61958-

100 mg

DISPENSER: Each time Zydelig

NDC 61958-

150 mg

DISPENSER: Each time Zydelig